Is it safe to combine sertraline (selective serotonin reuptake inhibitor (SSRI)) 200mg and duloxetine (serotonin-norepinephrine reuptake inhibitor (SNRI)) 60mg daily?

From the Guidelines

Combining sertraline 200mg and duloxetine 60mg daily is not recommended due to the risk of serotonin syndrome, a potentially life-threatening condition caused by excessive serotonin levels in the brain. Both medications increase serotonin levels - sertraline as a selective serotonin reuptake inhibitor (SSRI) and duloxetine as a serotonin-norepinephrine reuptake inhibitor (SNRI) - and taking them together can lead to dangerously high serotonin concentrations 1. Symptoms of serotonin syndrome include agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, tremor, excessive sweating, diarrhea, and in severe cases, seizures or loss of consciousness.

Key considerations when evaluating the safety of combining these medications include:

• The risk of serotonin syndrome, which can be triggered by combining serotonergic medications 1
• The importance of close medical supervision and careful dose adjustments if a healthcare provider is considering adding one medication to the other 1
• The need for alternative medication strategies that might be more appropriate for a specific condition, as suggested by a mental health provider

If you're currently taking one of these medications and a healthcare provider is considering adding the other, this should only be done under close medical supervision with careful dose adjustments. Never combine these medications without explicit medical guidance. If you're already taking both and experiencing symptoms like confusion, agitation, tremors, or fever, seek immediate medical attention. A mental health provider can suggest alternative medication strategies that might be more appropriate for your specific condition.

From the Research

Combination of Sertraline and Duloxetine

• The combination of sertraline (selective serotonin reuptake inhibitor (SSRI)) and duloxetine (serotonin-norepinephrine reuptake inhibitor (SNRI)) may increase the risk of serotonin syndrome, a potentially life-threatening condition caused by a toxic excess of serotonin 2, 3.
• Serotonin syndrome can be precipitated by the rapid titration of sertraline and other medications that increase serotonin production, release, or inhibit serotonin metabolism 2.
• The classic triad of serotonin syndrome includes neuromuscular excitation, autonomic instability, and altered mental status, and if left unrecognized and untreated, patients are at a high risk of mortality 2.

Dosing and Safety Considerations

• The optimal dose of sertraline for the treatment of depression is 50 mg daily, but it can be increased up to 200 mg daily for patients who do not show an adequate therapeutic response 4.
• There is no established safe dose for the combination of sertraline and duloxetine, and the risk of serotonin syndrome may be increased with higher doses of either medication 3, 5.
• Caution is needed when prescribing sertraline, especially in elderly patients, and when coadministering with other agents that may increase the risk of serotonin syndrome 5.

Clinical Evidence

• There are reports of serotonin syndrome induced by the combination of bupropion and SSRIs, which suggests that the combination of sertraline and duloxetine may also increase the risk of serotonin syndrome 3.
• A case report of a patient who developed serotonin syndrome after taking minimum doses of sertraline emphasizes the need for caution when prescribing sertraline, especially in elderly patients 5.
• Another study reported that the combination of venlafaxine (an SNRI) and SSRIs was well-tolerated in patients with depression who had a partial response to venlafaxine, but this does not necessarily apply to the combination of sertraline and duloxetine 6.